DNA Regions Research Articles

Characterization of telomere variant repeats using long reads enables allele-specific telomere length estimation.

Telomeres are regions of repetitive DNA at the ends of linear chromosomes which protect chromosome ends from degradation. Telomere lengths have been extensively studied in the context of aging and disease, though most studies use average telomere lengths which are of limited utility. We present a method for identifying all 92 telomere alleles from long read sequencing data. Individual telomeres are identified using variant repeats proximal to telomere regions, which are unique across alleles. This high-throughput and high-resolution characterization of telomeres could be foundational to future studies investigating the roles of specific telomeres in aging and disease.

Myxotrichum persicum sp. nov., and two new combinations in the genus Myxotrichum

We describe Myxotrichum persicum sp. nov. as a seed endophyte of Aegilops triuncialis in Lorestan province of Iran, using morphological traits and sequences of the internal transcribed spacer regions 1 and 2 including the intervening 5.8S nuclear ribosomal DNA (ITS) and partial nuclear 28S ribosomal DNA (LSU) regions. Myxotrichum persicum is differentiated from its closest relative, M. deflexum, by possessing smaller ascomata bearing much shorter, usually unbranched appendages, and smaller, ellipsoidal to fusiform, smooth-walled ascospores. Based on morphology and the multilocus phylogeny of ITS, LSU, MCM7 and RPB1, we herein propose to combine two species of Malbranchea, namely M. circinata and M. flavorosea, into the genus Myxotrichum as Myxotrichum circinatum and M. flavoroseum, respectively.

HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.

The Homeobox (HOX) gene family is essential to regulating cellular processes because it maintains the exact coordination required for tissue homeostasis, cellular differentiation, and embryonic development. The most distinctive feature of this class of genes is the presence of the highly conserved DNA region known as the homeobox, which is essential for controlling their regulatory activities. Important players in the intricate process of genetic regulation are the HOX genes. Many diseases, especially in the area of cancer, are linked to their aberrant functioning. Due to their distinctive functions in biomedical research-particularly in the complex process of tumor advancement-HOXA9 and HOXB9 have drawn particular attention. HOXA9 and HOXB9 are more significant than what is usually connected with HOX genes since they have roles in the intricate field of cancer and beyond embryonic processes. The framework for a focused study of the different effects of HOXA9 and HOXB9 in the context of tumor biology is established in this study.

CardioHotspots: a database of mutational hotspots for cardiac disorders.

Mutational hotspots are DNA regions with an abnormally high frequency of genetic variants. Identifying whether a variant is located in a mutational hotspot is critical for determining the variant's role in disorder predisposition, development, and treatment response. Despite their significance, current databases on mutational hotspots are limited to the oncology domain. However, identifying mutational hotspots is critical for any disorder in which genetics plays a role. This is true for the world's leading cause of death: cardiac disorders. In this work, we present CardioHotspots, a literature-based database of manually curated hotspots for cardiac diseases. This is the only database we know of that provides high-quality and easily accessible information about hotspots associated with cardiac disorders. CardioHotspots is publicly accessible via a web-based platform (https://genomics-hub.pros.dsic.upv.es:3099/). Database URL: https://genomics-hub.pros.dsic.upv.es:3099/.

A diversity of diversities: Do complex environmental effects underpin associations between below‐ and above‐ground taxa?

Abstract To predict how biodiversity will respond to global change, it is crucial to understand the relative roles of abiotic drivers and biotic interactions in driving associations between the biodiversity of disparate taxa. It is particularly challenging to understand diversity–diversity links across domains and habitats, because data are rarely available for multiple above‐ and below‐ground taxa across multiple sites. Here, we analyse data from a unique biodiversity data set gathered across a variety of oceanic temperate terrestrial habitats in Wales, comprising 300 sites with co‐located soil microbial, plant, bird and pollinator surveys along with climate and soil physicochemical information. Soil groups are analysed using metabarcoding of the 16S, ITS1 and 18S DNA regions, allowing in‐depth characterisation of microbial and soil animal biodiversity. We explore biodiversity relationships along three aspects of community composition: First, we assess correlation between the alpha diversity of different groups. Second, we assess whether biotic turnover between sites is correlated across different groups. Finally, we investigate the co‐occurrence of individual taxa across sites. In each analysis, we assess the contribution of linear or nonlinear environmental effects. We find that a positive correlation between alpha diversity of plants, soil bacteria, soil fungi, soil heterotrophic protists, bees and butterflies is in fact driven by complex nonlinear responses to abiotic drivers. In contrast, environmental variation did not account for positive associations between the diversity of plants and both birds and AM fungi, suggesting a role for biotic interactions. Both the diversity and taxon‐level associations between the differing soil groups remained even after accounting for nonlinear environmental gradients. Above‐ground, spatial factors played larger roles in driving biotic communities, while linear environmental gradients were sufficient to explain many group‐ and taxon‐level relationships. Synthesis. Our results show how nonlinear responses to environmental gradients drive many of the relationships between plant biodiversity and the biodiversity of above‐ and below‐ground biological communities. Our work shows how different aspects of biodiversity might respond nonlinearly to changing environments and identifies cases where management‐induced changes in one community could either influence other taxa or lead to loss of apparent biological associations.

Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction

Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction

Quantitative profiling of regulatory DNA activity at single-cell resolution.

Quantitative profiling of regulatory DNA activity at single-cell resolution.

Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research

Exhaustive efforts have been dedicated to uncovering genomic aberrations linked to cancer susceptibility. Noncoding sequence variants and epigenetic alterations significantly influence gene regulation and could contribute to cancer development. However, exploring noncoding regions in hereditary cancer susceptibility demands cutting-edge methodologies for functionally characterizing genomic discoveries. Additionally, comprehending the impact on cancer development of variants in noncoding DNA and the epigenome necessitates integrating diverse data through bioinformatic analyses. As novel technologies and analytical methods continue to advance, this realm of research is rapidly gaining traction. Within this mini-review, we delve into future research domains concerning aberrations in noncoding DNA regions, such as pseudoexons, promoter variants and cis-epimutations.

Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.

Senataxin is an evolutionarily conserved RNA-DNA helicase involved in DNA repair and transcription termination that is associated with human neurodegenerative disorders. Here, we investigated whether Senataxin loss affects protein homeostasis based on previous work showing R-loop-driven accumulation of DNA damage and protein aggregates in human cells. We find that Senataxin loss results in the accumulation of insoluble proteins, including many factors known to be prone to aggregation in neurodegenerative disorders. These aggregates are located primarily in the nucleolus and are promoted by upregulation of non-coding RNAs expressed from the intergenic spacer region of ribosomal DNA. We also map sites of R-loop accumulation in human cells lacking Senataxin and find higher RNA-DNA hybrids within the ribosomal DNA, peri-centromeric regions, and other intergenic sites but not at annotated protein-coding genes. These findings indicate that Senataxin loss affects the solubility of the proteome through the regulation of transcription-dependent lesions in the nucleus and the nucleolus.

A revised tribal classification of Papaveraceae (poppy family) based on molecular and morphological data

AbstractPapaveraceae, commonly known as the poppy family, contains many species with horticultural and/or pharmaceutical importance and has been the subject of various molecular studies. However, a widely accepted tribal classification for Papaveraceae remains lacking. In this study, we used a sampling covering all 48 of the currently recognized genera of Papaveraceae. Our study is to employ broad morphological data in combination with sequence data from two nuclear and seven plastid DNA regions to reconstruct phylogenetic relationships within the family. Our analyses indicate that Pteridophylloideae is sister to the clade containing Hypecooideae and Fumarioideae, and these three lineages are in turn sister to Papaveroideae. The alternative topologies constraining Pteridophylloideae as sister to the other poppy species, to Papaveroideae or to Hypecooideae, as recovered in previous studies, are all rejected. Fumarioideae contains nine main clades, and Fumarieae is nested in traditional Corydaleae. Within Papaveroideae, three main clades are recovered and Platystemoneae is embedded within traditional Papavereae. Both topologies constraining traditional Corydaleae or Papavereae as monophyletic are significantly rejected. Within this phylogenetic framework, the evolution of selected characters is inferred and diagnostic morphological characters at different taxonomic levels are identified and discussed. Based on morphological and molecular evidence, a new tribal classification of Papaveraceae is presented, in which 4 subfamilies, 14 tribes (including 7 newly described tribes), and 43 genera are recognized.

Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy

BackgroundDiabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA.MethodsTo identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle.ResultsOne significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity.ConclusionsOur results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Rapid molecular species identification of mammalian scat samples using nanopore adaptive sampling

Rapid molecular species identification of mammalian scat samples using nanopore adaptive sampling

Identification of a candidate gene for the I locus determining the dominant white bulb color in onion (Allium cepa L.).

Through a map-based cloning approach, a gene coding for an R2R3-MYB transcription factor was identified as a causal gene for the I locus controlling the dominant white bulb color in onion. White bulb colors in onion (Allium cepa L.) are determined by either the C or I loci. The causal gene for the C locus was previously isolated, but the gene responsible for the I locus has not been identified yet. To identify candidate genes for the I locus, an approximately 7-Mb genomic DNA region harboring the I locus was obtained from onion and bunching onion (A. fistulosum) whole genome sequences using two tightly linked molecular markers. Within this interval, the AcMYB1 gene, known as a positive regulator of anthocyanin production, was identified. No polymorphic sequences were found between white and red AcMYB1 alleles in the 4,860-bp full-length genomic DNA sequences. However, a 4,838-bp LTR-retrotransposon was identified in the white allele, in the 79-bp upstream coding region from the stop codon. The insertion of this LTR-retrotransposon created a premature stop codon, resulting in the replacement of 26 amino acids with seven different residues. A molecular marker was developed based on the insertion of this LTR-retrotransposon to genotype the I locus. A perfect linkage between bulb color phenotypes and marker genotypes was observed among 5,303 individuals of segregating populations. The transcription of AcMYB1 appeared to be normal in both red and white onions, but the transcription of CHS-A, which encodes chalcone synthase and is involved in the first step of the anthocyanin biosynthesis pathway, was inactivated in the white onions. Taken together, an aberrant AcMYB1 protein produced from the mutant allele might be responsible for the dominant white bulb color in onions.

Prevalence and molecular characterization of Hysterothylacium species infecting Pandora (Pagellus erythrinus) in the Mediterranean Sea of Egypt

Species of the genus Hysterothylacium are aquatic roundworms (nematodes) belonging to the family Raphidascarididae. Some species in this family are known to be associated with zoonotic diseases in humans after they consume their parasitic larvae in raw or undercooked fish. The aim of this research was to report the prevalence, morphology, and molecular characteristics of Hysterothylacium species in Pagellus erythrinus. A total of Two hundred fish were purchased from the fish market in Damanhour, Beheira Province, between December 2021 and November 2022 and subjected to examination. For molecular characterization, the internal transcribed spacer (ITS) region of nuclear ribosomal DNA and the mitochondrial cytochrome oxidase subunit 2 (COX-2) gene were used. Hysterothylacium species were morphologically described and identified from the intestine of Pagellus erythrinus in Beheira Province, Egypt. The PCR amplified 1087 bp and 629 bp of the target sequences of the ITS region and COX-2 gene, respectively. Sequence analysis revealed the Hysterothylacium thalassini species. The identified species provided novel biological data for the Hysterothylacium nematode in Pagellus erythrinus. The prevalence of Hysterothylacium species recovered from the intestine was 55%. The highest prevalence of 72% has been reported in summer compared to the lowest prevalence of 38% in the winter. Females had a higher prevalence of 61.8% than males, with 44.2%. The first detection, prevalence, and molecular characterization of H. thalassini in Pagellus erythrinus from Beheira Province, Egypt, was presented in this study.

Polymorphism rs117585797 of the ANO2 gene as a genetic marker of a high risk of developing combined proliferative diseases of the uterus in women with endometriosis

Introduction. Endometriosis is a common gynecological disease that has important socio-economic significance for both sick women, their families, and society as a whole. It is often combined with other hyperplastic diseases of the uterus.Aim. To analyze the involvement of GWAS-significant polymorphic loci of sex hormone genes in the development of combined proliferative diseases of the uterus in women with endometriosis. Materials and methods. The sample for the study included 395 women, including 103 patients with isolated endometriosis and 292 patients with endometriosis in combination with uterine fibroids and/or endometrial hyperplasia. All women underwent molecular genetic testing of seven GWAS-significant single-nucleotide polymorphic variants of sex hormone genes (rs34670419, rs11031005, rs11031002, rs148982377, rs112295236, rs1641549, rs117585797). The analysis of associations of polymorphic variants with the risk of developing combined proliferative diseases of the uterus in patients with endometriosis was carried out. To assess the functional effects of SNP associated with the formation of combined proliferative diseases of the uterus in women with endometriosis, the online programs HaploReg and Gtex Portal were used.Results and discussion. Genetic variant A rs117585797 of the ANO2 gene is a risk factor for the development of combined proliferative diseases of the uterus in women with endometriosis (p = 0.05, рperm = 0.05, OR = 4.29). According to the data obtained in silico, the rs117585797 locus localized in the intron of the ANO2 gene affects the affinity of the regulatory DNA motif to the transcription factors Crx and Gsc.Conclusions. Polymorphic locus rs117585797 of the ANO2 gene is associated with a high risk of the formation of combined proliferative diseases of the uterus in patients with endometriosis.

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients.

Decidualisation, the process whereby endometrial stromal cells undergo morphological and functional transformation in preparation for trophoblast invasion, is often disrupted in women with polycystic ovary syndrome (PCOS) resulting in complications with pregnancy and/or infertility. The transcription factor Wilms tumour suppressor 1 (WT1) is a key regulator of the decidualization process, which is reduced in patients with PCOS, a complex condition characterized by increased expression of androgen receptor in endometrial cells and high presence of circulating androgens. Using genome-wide chromatin immunoprecipitation approaches on primary human endometrial stromal cells, we identify key genes regulated by WT1 during decidualization, including homeobox transcription factors which are important for regulating cell differentiation. Furthermore, we found that AR in PCOS patients binds to the same DNA regions as WT1 in samples from healthy endometrium, suggesting dysregulation of genes important to decidualisation pathways in PCOS endometrium due to competitive binding between WT1 and AR. Integrating RNA-seq and H3K4me3 and H3K27ac ChIP-seq metadata with our WT1/AR data, we identified a number of key genes involved in immune response and angiogenesis pathways that are dysregulated in PCOS patients. This is likely due to epigenetic alterations at distal enhancer regions allowing AR to recruit cofactors such as MAGEA11, and demonstrates the consequences of AR disruption of WT1 in PCOS endometrium.

Comparative Analysis of 1,9-Dimethyl-Methylene Blue and Toluidine Blue Interactions with ct-DNA, G-Quadruplex DNA, and ssDNA

This study presents a comprehensive investigation into the interactions of two distinct synthetic dyes—1,9-Dimethyl-Methylene Blue and Toluidine Blue —with different DNA structures, namely calf thymus DNA (ct-DNA), G-quadruplex DNA, and single stranded DNA (ssDNA). The objective of this research is to elucidate the molecular affinities of these dyes for specific DNA structures and explore their potential applications in molecular biology and diagnostics. The experimental approach involved detailed UV-visible spectroscopic analyses, to probe the binding affinities of each dye with ct-DNA, G-quadruplex DNA, and ssDNA. The study aimed to assess the selectivity of these dyes towards the unique structural features of each DNA entity. The binding stoichiometry is defined from Job’s method. The selectivity of the dyes towards DNA also investigated with competitive dialysis experiments. The binding stoichiometry were 1:1 for 1,9-Dimethyl-Methylene Blue and Toluidine Blue and G-quadruplex DNA or ssDNA. Besides, results indicate that 1,9-Dimethyl-Methylene Blue and Toluidine Blue exhibit a pronounced affinity for G-quadruplex DNA, and ct-DNA. While single-stranded DNA is a fundamental component of DNA replication and transcription, our dyes exhibit lower affinity for this structure. The selectivity is advantageous, as it allows for the discrimination between single-stranded and structured DNA regions. The potential applications in studying DNA dynamics and unwinding processes are vast.

Molecular Identification and Phylogenetic Analysis of Cymbidium Species (Orchidaceae) Based on the Potential DNA Barcodes matK, rbcL, psbA-trnH, and Internal Transcribed Spacer

Numerous Cymbidium species have significant commercial value globally due to their exotic ornamental flowers. Identifying Cymbidium species is challenging due to their similar shapes, which hinders their rational use and the conservation of germplasm resources. In the present study, firstly, four plastid loci (matK, rbcL, psbA-trnH, and atpF-atpH) and a nuclear locus (internal transcribed spacer, ITS) were initially examined to identify Cymbidium species. Secondly, we inferred the interspecific phylogeny of Cymbidium species using ITS sequences. All of these DNA regions, with the exception of atpF-atpH, could be readily amplified from Cymbidium, and the corresponding DNA sequences can be successfully obtained by sequencing. Our research demonstrated that ITS exhibited the highest intra- and interspecific divergences, the greatest barcoding gap, and the highest proportion of species identification. The phylogenetic analysis of Cymbidium species based on the ITS regions primarily corroborated the results obtained using traditional morphological methods. A comparative analysis of candidate DNA barcodes has shown that the ITS can be used not only for barcoding Cymbidium species but also for the phylogenetic analysis of Cymbidium.

Characterisation of Nematoda and Digenea in selected Australian freshwater snails

Freshwater snails are integral to local ecosystems as a primary food source for various vertebrate species, thereby contributing significantly to ecological food webs. However, their role as intermediate hosts also makes them pivotal in the transmission of parasites. In Australia, research on freshwater snails has predominantly focused on their role as intermediate hosts for livestock parasites, while there has been limited exploration of the impact of these parasites on snail health and population dynamics. The aim of this study was to determine parasitic infection in freshwater snails. This study was conducted in the south-eastern region of Australia, in 2022. A total of 163 freshwater snails from four different species were collected and examined in the Murrumbidgee catchment area in the southeastern part of Australia during the Southern Hemisphere summer and autumn months (February to May). The species included Isidorella hainesii, Glyptophysa novaehollandica, Bullastra lessoni (endemic species), and Physella acuta (an introduced species). Through the analysis of sequence data from the various regions of the nuclear ribosomal DNA, we determined that the Digenea species in this study belonged to three distinct species, including Choanocotyle hobbsi, Petasiger sp. and an unidentified species belonging to Plagiorchioidea. Additionally, analysis of the sequences from Nematoda found in this study, revealed they could be categorized into two separate taxa, including Krefftascaris sp. and an unidentified nematode closely associated with plant and soil nematodes. This research holds significant implications for the future understanding and conservation of Australian freshwater ecosystems. Most parasites found in the present study complete their life cycle in snails and turtles. As many of freshwater snail and turtle species in Australia are endemic and face population threats, exploring the potential adverse impacts of parasitic infections on snail and turtle health, is crucial for advancing our understanding of these ecosystems and also paving the way for future research and conservation efforts. While none of the native snail species in the present study have been listed as endangered or threatened, this may simply be attributed to the absence of regular population surveys.

Mechanisms of vibration-induced structural myocardial remodeling

The review analyzes literature data on structural changes in the heart of patients with vibration disease, as detected by echocardiographic methods. Particularly, it highlights concentric remodeling of the left ventricle chambers and disturbances in diastolic function. The review also discusses a 1.2-fold decrease in heart structure intensity compared to healthy individuals (p 0.05). Furthermore, it examines changes in morphometric and bioenergetic parameters of cardiomyocytes under different experimental vibration modes (7 and 56 sessions at a frequency of 8 Hz), confirming the disruptions in the relationship between the spatial configuration of the heart cavities, contractile ability, and energy supply potential. Loss of cardiac myofibrils represents the transition from myocardial hypertrophy to decompensation, accompanied by an increase in degenerative (dystrophic) signs such as the loss of sarcomeres in cardiomyocytes. Understanding these pathological (morphological) processes requires consideration of various mediators that regulate cell metabolism, proliferation, growth, and survival, including stromal interaction molecule, calcium ATPase of the endo(sarco)plasmic reticulum, inositol-1,4,5-triphosphate receptor, protein that forms CRAC channels, and transient receptor potential canonical. The degradation system of the extracellular matrix, including matrix metalloproteinases and tissue inhibitors, plays a crucial role in structural cardiac remodeling. This system regulates the rate of mRNA synthesis on the DNA matrix by binding to specific DNA regions that control cardiac nutrition and plasticity. The review suggests that these findings can help explain some patterns of cardiac remodeling development in patients with vibration disease and determine the direction of pathogenetically based therapy. This therapy should consider not only the vibration-protective effect of drugs but also their ability to inhibit and regress myocardial remodeling.